Efficacy and Safety of Adalimumab Plus Medium Dose Oral Glucocorticosteroid for Refractory Behçet's Uveitis

NCT ID: NCT05105347

Last Updated: 2021-11-03

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 130 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-11-10
• Study Completion Date: 2026-12-31

Brief Summary

This study is a multi-center randomized non-inferiority study that aims to observe the short-term (3 months) efficacy and safety of adalimumab plus medium-dose glucocorticosteroid (30mg/d prednisone or equivalent) with slow tapering for recurrent Behçet's uveitis (BU) attack compared with adalimumab plus high-dose glucocorticosteroid (60mg/d prednisone or equivalent) with slow tapering.

Detailed Description

According to the most recent European League Against Rheumatism (EULAR) recommendation, patients presenting with an initial or recurrent episode of acute sight-threatening uveitis should be treated with high-dose glucocorticoids, infliximab or interferon-α. Adalimumab, another TNFα antagonist, is also considered as an alternative for infliximab and have proved its efficacy in several RCTs in the treatment of non-infectious intermediate, posterior and pan-uveitis. As higher dose glucocorticosteroid have greater side effects, this study aims to evaluate the non-inferior efficacy and safety of adalimumab plus medium-dose glucocorticosteroid compared with adalimumab plus high-dose glucocorticosteroid (and slow tapering) for recurrent posterior or pan-uveitis attack of Behcet's uveitis. Refractory BU is defined as relapse of posterior or panuveitis with at least 10mg daily prednisone (or equivalent). The acute attack will be controlled with adalimumab (80mg once, 40mg q2w thereafter) plus medium dose initial oral glucocorticosteroid (30mg daily prednisone or equivalent) in the "medium dose" group or plus high dose oral glucocorticosteroid (60mg daily prednisone or equivalent) in the "high dose" group with fixed tapering protocols. Patients will be followed up at 2w, 4w, 8w, and 12w after initiation of treatment. The primary endpoint is the inflammatory control rate. Secondary endpoints are BCVA, vascular leakage score on fundus fluorescein angiography (FFA), BOS 24 score and uveitis deterioration rate. The safety profiles of both groups will be also monitored.

Conditions

Uveitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Medium dose group (Adalimumab plus medium dose oral glucocorticosteroid)

Patients will be given adalimumab with 30mg daily prednisone or equivalent with a fixed slow tapering plan.

Group Type: EXPERIMENTAL

Adalimumab plus different doses of oral glucocorticosteroid

Intervention Type: DRUG

A loading dose of 80mg adalimumab will be given subcutaneously and then change to 40mg adalimumab every two weeks. Medium dose oral glucocorticosteroid (30mg/d prednisone or equivalent) will be given to the experimental dose group and high dose oral glucocorticosteroid (60mg/d prednisone or equivalent) will be given to the high dose group.

High dose group (Adalimumab plus high dose oral glucocorticosteroid)

Patients will be given adalimumab with 60mg daily prednisone or equivalent with a fixed slow tapering plan.

Group Type: ACTIVE_COMPARATOR

Adalimumab plus different doses of oral glucocorticosteroid

Intervention Type: DRUG

A loading dose of 80mg adalimumab will be given subcutaneously and then change to 40mg adalimumab every two weeks. Medium dose oral glucocorticosteroid (30mg/d prednisone or equivalent) will be given to the experimental dose group and high dose oral glucocorticosteroid (60mg/d prednisone or equivalent) will be given to the high dose group.

Interventions

Adalimumab plus different doses of oral glucocorticosteroid

A loading dose of 80mg adalimumab will be given subcutaneously and then change to 40mg adalimumab every two weeks. Medium dose oral glucocorticosteroid (30mg/d prednisone or equivalent) will be given to the experimental dose group and high dose oral glucocorticosteroid (60mg/d prednisone or equivalent) will be given to the high dose group.

Intervention Type: DRUG

Other Intervention Names

Humira, prednisone

Eligibility Criteria

Inclusion Criteria

• Behçet's disease (BD) patients fulfilling the International Criteria for Behçet's disease (ICBD) published in 2013 with recent recurrence of pan- or posterior uveitis
• The patient should be on ≥10mg/d oral prednisone or equivalent

Exclusion Criteria

• Previous treatment with TNFα inhibitors within 3 months
• Pregnancy, breast feeding women
• Malignancy
• Heart failure
• Demyelinating diseases
• Renal impairment (creatinine > 1.5 mg/dl)
• Depression or other psychic disorders
• History of acute or chronic inflammatory joint or autoimmune disease
• Patients with severe extra-ocular involvement other than oral/genital ulcer and skin involvement
• Organ or bone marrow transplant recipient, cardiac failure > NYHA III
• Acute liver disease with ALT or SGPT 2x above normal
• White blood cell count < 3500/mm^3
• Platelet count < 100000/mm^3
• Hgb < 8.5g/dl
• T-SPOT TB: ≥200 SFCs per 10^6 PBMC
• Active peptic ulcer, systemic or local infection, moderate to severe osteoporosis or other contraindications of intermediate dose corticosteroids
• Other severe ocular diseases or intraocular surgery within 3 months
• Media opacity precluding a clear view of the fundus
• Positive screen test for HBV, HCV, HIV infection or syphilis
• Body weight <45 kg
• Alcohol abuse or drug abuse
• Mental impairment
• Uncooperative attitude

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Peking Union Medical College Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Central Contacts

Hang Song, MD

Role: CONTACT

Phone: +8615600612346

Email: songhang_pumch@163.com

Chan Zhao, MD

Role: CONTACT

Phone: +8613810454083

Email: zhaochan@pumch.cn

References

Jaffe GJ, Dick AD, Brezin AP, Nguyen QD, Thorne JE, Kestelyn P, Barisani-Asenbauer T, Franco P, Heiligenhaus A, Scales D, Chu DS, Camez A, Kwatra NV, Song AP, Kron M, Tari S, Suhler EB. Adalimumab in Patients with Active Noninfectious Uveitis. N Engl J Med. 2016 Sep 8;375(10):932-43. doi: 10.1056/NEJMoa1509852.

Reference Type: BACKGROUND

PMID: 27602665 (View on PubMed)

Levy-Clarke G, Jabs DA, Read RW, Rosenbaum JT, Vitale A, Van Gelder RN. Expert panel recommendations for the use of anti-tumor necrosis factor biologic agents in patients with ocular inflammatory disorders. Ophthalmology. 2014 Mar;121(3):785-96.e3. doi: 10.1016/j.ophtha.2013.09.048. Epub 2013 Dec 17.

Reference Type: BACKGROUND

PMID: 24359625 (View on PubMed)

Vallet H, Riviere S, Sanna A, Deroux A, Moulis G, Addimanda O, Salvarani C, Lambert M, Bielefeld P, Seve P, Sibilia J, Pasquali J, Fraison J, Marie I, Perard L, Bouillet L, Cohen F, Sene D, Schoindre Y, Lidove O, Le Hoang P, Hachulla E, Fain O, Mariette X, Papo T, Wechsler B, Bodaghi B, Rigon MR, Cacoub P, Saadoun D; French Behcet Network. Efficacy of anti-TNF alpha in severe and/or refractory Behcet's disease: Multicenter study of 124 patients. J Autoimmun. 2015 Aug;62:67-74. doi: 10.1016/j.jaut.2015.06.005. Epub 2015 Jul 8.

Reference Type: BACKGROUND

PMID: 26162757 (View on PubMed)

Kaburaki T, Namba K, Sonoda KH, Kezuka T, Keino H, Fukuhara T, Kamoi K, Nakai K, Mizuki N, Ohguro N; Ocular Behcet Disease Research Group of Japan. Behcet's disease ocular attack score 24: evaluation of ocular disease activity before and after initiation of infliximab. Jpn J Ophthalmol. 2014 Mar;58(2):120-30. doi: 10.1007/s10384-013-0294-0. Epub 2014 Jan 31.

Reference Type: BACKGROUND

PMID: 24482146 (View on PubMed)

Other Identifiers

42-ZS-2925

Identifier Type: -

Identifier Source: org_study_id